Project Summary Opioid use by older adolescents and young adults (AYAs; ages 16-30) is a significant public health concern requiring scalable approaches to prevent opioid misuse and opioid use disorders (OUDs). A unique feature of the opioid crisis is the rapidly morphing clinical sequela, which includes changes in opioids used based on evolving access to prescription medicines (e.g., due to rescheduling, prescription drug monitoring programs), availability of street opioids and new formulations (e.g., illicitly made fentanyl), and varying routes of administration associated with escalation in use (e.g., oral, snorting, injection). A health care visit provides an access point to identify and intervene with AYAs at risk for opioid misuse/OUD to alter risk trajectories. The emergency department (ED) is an ideal venue to reach AYAs, particularly as young adults may disconnect from primary care when transitioning out of pediatric medicine. The ED is also common source of opioid prescriptions. Despite promising findings from our prior work on efficacious ED brief interventions (BIs) that reduced opioid misuse/overdose risk, and other substance use (secondary analyses of our alcohol BI reduced prescription drug misuse), modest effect sizes limit the public health impact of one-session BIs. Further, we lack critical data on how to extend interventions for maximal impact, with parsimony of resources and ease of implementation in healthcare settings. The proposed study will evaluate the efficacy of interventions of varying type/intensity, tested using a four group randomized controlled trial design. The proposed work leverages technology that is appealing to AYAs to facilitate intervention delivery by health coaches (HCs), promoting fidelity along with real-time tailoring in accordance with the rapidly changing opioid landscape. The specific aims are to: 1) adapt promising HC-delivered interventions and pilot test feasibility/acceptability in AYAs (UG3); 2) evaluate the efficacy of interventions and their combinations on preventing/reducing opioid misuse and OUD among AYAs (UH3); and 3) examine ED implementation and sustainability, including economic evaluation (UH3). Secondary aims are to examine efficacy on other substance use, and moderators (e.g., sex, motives, opioid risk severity) and mediators (e.g., self-efficacy, motivation to change) of outcome. AYAs (ages 16-30; N=1170) in the ED screening positive for opioid use (+ >1 risk factor) or misuse will be stratified by risk severity and sex and randomly assigned to one of two ED-based conditions [(Check-In BI delivered by HC via remote video chat, or enhanced usual care brochure (EUC)], with or without HC messaging via web portal (Check-In Portal for 4 weeks). Thus, the four conditions are: EUC only, BI only, Portal Only, BI + Portal, with outcomes measured at 4-, 8-, and 12-months. This study is innovative by testing the efficacy of interventions to prevent/reduce opioid misuse/OUD, which are feasible to implementation in healthcare systems. Technology- driven, scalable interventions via HC delivery allow for real-time tailoring to the rapidly changing opioid epidemic, which could have high, sustainable impact on preventing escalation of opioid misuse among AYAs.